Vitamin D Deficiency, Interleukin 17, and Vascular Function in Rheumatoid Arthritis

OBJECTIVE: Vitamin D deficiency is associated with increased cardiovascular (CV) disease risk in the general population. We examined the association between vitamin D deficiency and CV risk in rheumatoid arthritis (RA). METHODS: We measured large artery compliance by pulse wave velocity and microvascular function by the reactive hyperemia index in patients with stable RA (n = 87). We quantified CV risk factors, serum 25-hydroxyvitamin D [25(OH)D], and interleukin 17 (IL-17), and RA disease activity by Disease Activity Score of 28 joints. We used linear regression to test associations between serum 25(OH)D and CV risk factors. RESULTS: The mean serum 25(OH)D level in the cohort was 27.1 ± SD 13.6 ng/ml. Fifty-nine patients (68%) were vitamin D-insufficient (25(OH)D < 30 ng/ml; mean 20.2 ± 5.9 ng/ml) and of these, 25 (29%) were vitamin D-deficient (25(OH)D < 20 ng/ml; mean 14.4 ± 3.4 ng/ml). In the whole cohort and the vitamin D-insufficient group, serum 25(OH)D was inversely associated with IL-17 (log IL-17; β = -0.83, p = 0.04; β = -0.63, p = 0.004, respectively) by univariate analysis, which persisted after adjustment for season, and in multivariate analysis after adjustment for confounders (log IL-17; β = -0.74, p = 0.04; β = -0.53, p = 0.02). In vitamin D-deficient patients, serum 25(OH)D was positively associated with microvascular function by univariate and multivariate analysis after adjustment for confounders (β = 2.1, p = 0.04; β = 2.7, p = 0.04). CONCLUSION: Vitamin D deficiency in RA may affect Th17 responses and microvascular function. Maintaining normal serum vitamin D levels may protect against IL-17-mediated inflammation and vascular dysfunction in RA.